chr16-22814899-C-G

Variant names:

• chr16-22814899-C-G
• rs1473627973
• NM_006043.2:c.289C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006043.2(HS3ST2):​c.289C>G​(p.Arg97Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: HS3ST2 NM_006043.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.57
• Publications: 0 publications found

Genes affected

HS3ST2 (HGNC:5195): (heparan sulfate-glucosamine 3-sulfotransferase 2) Heparan sulfate biosynthetic enzymes are key components in generating a myriad of distinct heparan sulfate fine structures that carry out multiple biologic activities. The enzyme encoded by this gene is a member of the heparan sulfate biosynthetic enzyme family. It is a type II integral membrane protein and possesses heparan sulfate glucosaminyl 3-O-sulfotransferase activity. This gene is expressed predominantly in brain and may play a role in the nervous system. [provided by RefSeq, Jul 2008]

ENSG00000283213 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0931052).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006043.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HS3ST2	NM_006043.2	MANE Select	c.289C>G	p.Arg97Gly	missense	Exon 1 of 2	NP_006034.1	Q9Y278

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HS3ST2	ENST00000261374.4	TSL:1 MANE Select	c.289C>G	p.Arg97Gly	missense	Exon 1 of 2	ENSP00000261374.3	Q9Y278
	HS3ST2	ENST00000473392.1	TSL:5	n.289C>G		non_coding_transcript_exon	Exon 1 of 4	ENSP00000454505.1	H3BMR2
	ENSG00000283213	ENST00000636354.2	TSL:5	n.-103G>C		upstream_gene	N/A

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	17
DANN	Benign	0.81
DEOGEN2	Benign	0.027	T
Eigen	Benign	-0.96
Eigen_PC	Benign	-0.96
FATHMM_MKL	Benign	0.27	N
LIST_S2	Benign	0.56	T
M_CAP	Benign	0.071	D
MetaRNN	Benign	0.093	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	L
PhyloP100		1.6
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-0.62	N
REVEL	Benign	0.038
Sift	Benign	0.27	T
Sift4G	Benign	0.42	T
Polyphen		0.0	B
Vest4		0.27
MutPred		0.21		Gain of relative solvent accessibility (P = 0.005)
MVP		0.27
MPC		1.3
ClinPred		0.15	T
GERP RS		1.6
Varity_R		0.068
gMVP		0.58

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1473627973; hg19: chr16-22826220;